DESCRIPTION (investigator's abstract): The goal of this project is to characterize the expression profile and signaling pathways of mouse TLRs 1-6. We plan to examine the expression of TLRs 1-6 in various cell types of the immune system, including dendritic cells and their subtypes, macrophages, and T and B lymphocytes and their subtypes. We will look for changes in TLR expression associated with activation of these cell types by various stimuli, such as pro-and anti-inflammatory cytokines. Our main emphasis will be on the analysis of TLR expression in various subpopulations of dendritic cells. We also plan to investigate the signaling pathways activated by different TLRs. We have recently identified several novel gene products involved in mammalian Toll signaling, and we plan to characterize them in detail. We also found differences in the signaling pathways activated by individual members of the Toll family. We plan to further investigate the similarities and differences in the signal transduction pathways activated by the individual TLRs and to analyze in detail the mechanisms that account for these differences. We will investigate where the differences in the signaling pathways lead to the induction of distinct target genes, and how this is related to the expression profile of individual TLRs. Our ultimate goal is to understand whether activation of different TLRs results in the induction of distinct cellular and immune responses.